高血压的治疗：新的循环医学证据

高血压治疗

新的循证医学证据华中科技大学协和医院心内科廖玉华高血压治疗：新的循证医学证据ADVANCE研究—固定复方制剂VALIDD研究—降压与心室舒张功能Ameta-analysisofRCTs中国人高血压临床试验证据ADVANCE研究:

在11,140例2型糖尿病患者中进行的降压与强化血糖控制的析因随机临床试验培哚普利吲达帕胺固定复方制剂（百普乐）对重要血管事件的影响Inclusioncriteria

Type2diabetesmellitusAge55yearsorolderAdditionalriskofvasculareventAge

65yearsHistoryofmajormacrovasculardiseaseHistoryofmajormicrovasculardiseaseFirstdiagnosisofdiabetes>10yearspriortoentryOthermajorriskfactorHypertensiveornormotensiveRandomisedstudytreatmentsBloodpressureloweringDouble-blindperindopril-indapamide

versusmatchingplacebo2.0/0.625mgorplaceboforfirst3months4.0/1.25mgorplacebothereafterBloodglucoselowering(ongoing)Open-labelgliclazideMR-basedintensivetherapytargetinganHbA1cof6.5%versususualguideline-basedcareAmongpatientswithdiabetes,doesbloodpressureloweringtherapy:Produceadditionalbenefitswhensystolicpressureisloweredbelow145mmHg?Producesimilarbenefitsforhypertensiveandnon-hypertensivepatients?AddtothebenefitsproducedbyothercardiovascularpreventivetherapiesincludingACEinhibitors?ADVANCEstudyhypotheses

Perindopril-indapamidearmADVANCE

Trialprofile12877withtype2diabetesregistered11140randomised5569assignedperindopril-indapamidecombination1737withdrewduringrun-inScheduledendoffollow-up:4.3years4908(88%)assessedatfinalvisit4081(73%)adherenttotreatment4losttofollow-up11losttofollow-upScheduledendoffollow-up:4.3years4863(87%)assessedatfinalvisit4143(74%)adherenttotreatment5571assignedmatchingplacebo血压降低情况Δ2.2mmHg(95%CI2.0-2.4);p<0.001Δ

5.6mmHg(95%CI5.2-6.0);p<0.001DiastolicSystolic安慰剂组培哚普利/吲达帕胺组MeanBloodPressure(mmHg)65758595105115125135145155165Follow-up(Months)R6121824303642485460140.3mmHg134.7mmHgAverageBPduringfollow-up77.0mmHg74.8mmHg全因死亡率Follow-up(months)01006121824303642485460

安慰剂组

培哚普利/吲达帕胺组Cumulativeincidence(%)Relativeriskreduction14%:95%CI2-25%p=0.0255死亡分析心血管死亡Follow-up(months)6121824303642485460安慰剂组培哚普利/吲达帕胺组非心血管死亡Follow-up(months)6121824303642485460安慰剂组培哚普利/吲达帕胺组相对危险降低18%;p=0.027相对危险降低8%;p=0.415%5%Cumulativeincidence(%)Coronaryevents*2P=0.02†Non-fatalMIordeathfromcoronaryheartdisease‡Unstableanginarequiringhospitalisation,coronaryrevascularisationorsilentMIMajorcoronaryheartdisease†26529411%(-6to24)Allcoronaryheartdisease468535

14%(2to24)Othercoronaryheartdisease‡28332414%(-1to27)*NumberofeventsPer-IndPlacebo(n=5,569)(n=5,571)Relativeriskreduction(95%CI)FavoursPer-IndFavoursPlaceboHazardratio0.51.02.0CerebrovasculareventsMajorcerebrovasculardisease†2152182%(-18to19)Allcerebrovasculardisease2863036%(-10to20)Othercerebrovasculardisease‡799921%(-6to41)2.0**2P=0.40†Non-fatalstrokeordeathfromcerebrovasculardisease‡TransientischaemicattackorsubarachnoidhaemorrhageNumberofeventsPer-IndPlacebo(n=5,569)(n=5,571)Relativeriskreduction(95%CI)FavoursPer-IndFavoursPlaceboHazardratio0.51.0Renalevents2.0Hazardratio0.51.0Neworworseningnephropathy18121618%(-1to32)Newmicroalbuminuria1094131721%(14to27)Totalrenalevents1243150021%(15to27)**2P=<0.01NumberofeventsPer-IndPlacebo(n=5,569)(n=5,571)Relativeriskreduction(95%CI)FavoursPer-IndFavoursPlacebo经过5年治疗可预防事件数:每治疗患者例数1例主要血管事件66例1例死亡79例1例冠脉事件75例1例肾脏事件*20例*多为新发微量白蛋白尿常规使用培哚普利与吲达帕胺的绝对获益总结2型糖尿病患者常规使用培哚普利/吲达帕胺治疗的结果:总死亡率降低14%心血管死亡降低18%主要血管事件降低9%总冠脉事件降低14%总肾脏事件降低21%这些获益在所有主要亚组都相似。治疗的耐受性非常好，副作用很少，遵从治疗的情况与安慰剂组相似。Amongpatientswithdiabetes,doesbloodpressureloweringtherapy:Produceadditionalbenefitswhensystolicpressureisloweredbelow145mmHg?Producesimilarbenefitsforhypertensiveandnon-hypertensivepatients?AddtothebenefitsproducedbyothercardiovascularpreventivetherapiesincludingACEinhibitors?Bloodpressureloweringindiabetes:

Unresolvedissues2000YESYESYESVALIDD研究TheInfluenceofAngiotensinReceptorBlockersandBloodPressureLoweringonDiastolicFunctioninPatientswithHypertensionandDiastolicDysfunction:TheVALsartanInDiastolicDysfunction

血管紧张素受体拮抗剂(ARB)对高血压和舒张功能不全患者的作用

SolomonS.AmericanCollegeofCardiology2007ScientificSessions,March25,2007.研究目的目的:验证下列假说是否正确“ARB较其他非阻断RAAS系统的降压药物更有效改善左室舒张功能”？SolomonS.AmericanCollegeofCardiology2007ScientificSessions,March25,2007.研究设计482例初选患者年龄大于45岁、1、2级高血压、无心功能不全病史组织多普勒检查，评价心肌舒张速度，确定舒张功能不全的存在384例舒张功能不全的患者缬沙坦组(n=186)320mg/d非RAAS拮抗剂降压治疗(n=198)钙拮抗剂、利尿剂、ß阻滞剂随机分组观察终点38周前后的舒张速度、等容舒张时间（S’)、加速时间、E/A、E/E’左室容积质量、射血分数随访38周SolomonS.AmericanCollegeofCardiology2007ScientificSessions,March25,2007.ARBvs.非RAAS阻断剂组:降压幅度相当38周后,两组的血压较基线相比降低幅度没有显著差异收缩压较基线的改变(mmHg)缬沙坦组(n=186)非RAAS阻断剂组(n=198)p=NS

SolomonS.AmericanCollegeofCardiology2007ScientificSessions,March25,2007.ARBvs.非RAAS阻断剂组:改善舒张功能疗效相当38周后,ARB和非RAAS阻断类降压药物均显著改善舒张功能，疗效相当时间/治疗前后的变化心肌舒张速度(cm/s)缬沙坦(n=186)非RAAS阻断剂组(n=198)基线7.57.5治疗38周后8.1*8.0*心肌舒张速度提高0.66**0.44*每组治疗前后比较P<0.0001,**组间比较P=NSSolomonS.AmericanCollegeofCardiology2007ScientificSessions,March25,2007.研究结论轻中度高血压患者虽然左室肥厚发生率低，但已经存在心肌舒张功能不全，这是高血压靶器官受累的早期标志，进而将导致左室肥厚在降压疗效相同时，ARB和非RAAS阻断类降压药物均显著改善心肌舒张功能，疗效相同降压治疗带来又一项收益，即改善舒张功能。即便是轻中度高血压患者，也可受益SolomonS.AmericanCollegeofCardiology2007ScientificSessions,March25,2007.VALIDD评论50%高血压患者存在舒张功能不全，虽然部分患者最终进展为心衰，但是迄今仍然没有具备针对性的治疗方法。VALIDD研究证实降低血压可有效改善舒张功能不全，即使轻中度高血压患者也可获益。这一结果说明：对于高血压患者，应该采取积极降压措施－－DrScottSolomon，VALIDD研究领导人，布莱根女子医院，哈佛医学院PreventionofstrokeandMIbyamlodipineandARBs氨氯地平与ARBs预防卒中与心肌梗死Ameta-analysisofRCTs随机对照临床试验综合分析WangJGetal.Hyp